Preparation of 2-keto carboxylic acid from carbon dioxide

ABSTRACT

The invention discloses a novel method for the preparation of a 2 keto carboxylic acid from carbon dioxide by an enzymatic addition reaction with an aldehyde compound. Carbon dioxide, which can be in the form of carbonate ions, is reacted with an aldehyde compound such as acetaldehyde and propionaldehyde under mild reaction conditions in the presence of a decarboxylase to give a 2-keto carboxylic acid such as pyruvic and a 2-ketobutyric acid by a reverse reaction to the enzymatic decarboxylation reaction. The scope of the invention involves contribution to a solution of the environmental problem of global warming due to carbon dioxide as a greenhouse effect gas in the aerospace.

TECHNICAL FIELD

[0001] The present invention relates to a method for the preparation ofa 2-keto carboxylic acid, which can readily be converted into acorresponding carboxylic acid, from carbon dioxide or, moreparticularly, to a method for the preparation of a 2-keto carboxylicacid by utilizing carbon dioxide, which is a potential environmentalpollutant, as an effective chemical resource.

BACKGROUND ART

[0002] As a countermeasure to the serious environmental problem ofglobal warming, it is required in recent years to substantiallydecreasing the greenhouse effect by various so-called greenhouse gasesof which carbon dioxide is one of the most notorious pollutant gases.Reducing of carbon dioxide in the aerospace can be accomplished bydecreasing emission of the gas but can also be accomplished byincreasing fixation or immobilization of the carbon dioxide gas fromemission sources.

[0003] A great variety of proposals are made heretofore for the ways offixation of carbon dioxide in an emission source including absorption inthe oceanic water, electrochemical reactions for the synthesis ofhydrocarbon compounds such as methane or alcoholic compounds such asmethanol from carbon dioxide, quasi-photosynthesis reaction for thesynthesis of methanol and so on. Though limited to a laboratory scaleexperimentation, a method has been developed for the fixation of carbondioxide gas to produce a carboxylic acid by a quasi-enzymatic reactionin the presence of a metal complex catalyst or in an organic synth sisreaction.

[0004] It is a general tr nd in recent years in this regard that certainenzymatic reactions have made their second debut by virtue of theiradvantages of the relatively small load imposed on the environment. Thisadvantage of low load on the environment, however, can hardly beobtained in the fixation of carbon dioxide according to the abovementioned various methods because of the considerably large energyconsumption in the methods and indispensability of using an organicsolvent in the reactions.

[0005] A report is also available of utilization of an enzymaticreaction for fixation of carbon dioxide. The enzymatic reaction so fardeveloped, however, is limited to the enhancement of water-solubility ofcarbon dioxide by means of a carbonate dehydratase.

BRIEF DESCRIPTION OF THE DRAWING

[0006]FIG. 1 is a bar chart showing the pH-dependency of the yield ofpyruvic acid produced in Example 1.

[0007]FIG. 2 is a bar chart showing the dependency of the yield of thepyruvic acid product on the concentration of the sodium carbonate buffersolutions prepared in Example 2.

DISCLOSURE OF INVENTION

[0008] The present invention accordingly has an object to provide ameans for the synthetic preparation of a low molecular-weight 2-ketocarboxylic acid compound from carbon dioxide as a chemical resource toserve as a starting material by utilizing a specific enzymatic reactionwhich is not liable for a heavy load imposed on the environment.

[0009] Thus, the method provided by the present invention for thesynthetic preparation of a 2-keto carboxylic acid from carbon dioxide asa starting reactant comprises the step of reacting carbon dioxide withan aldehyde compound in the presence of a decarboxylase to effect anaddition reaction which is a reverse reaction to the enzymaticdecarboxylation reaction f a 2-ket carboxylic acid.

[0010] The form of the carbon dioxid used to pertain to thabove-described inventive method is not particularly limitative and canbe any of gaseous carbon dioxide, liquefied carbon dioxide,supercritical carbon dioxide and carbonate ions.

[0011] As is mentioned above, the enzymatic addition reaction proceedingin the inventive method between carbon dioxide and an aldehyde compoundis a reverse reaction to the decarboxylation reaction proceeding in thepresence of a decarboxylase. The carbon dioxide to pertain to theinventive method can be, besides the gaseous, liquid and supercriticalforms, in the form of carbonate ions as is the case in an aqueoussolution of a water-soluble carbonate compound as in a sodiumcarbonate-based buffer solution.

[0012] The 2-keto carboxylic acid compound as the reaction product ofthe inventive method naturally differs depending on the aldehydecompound to be reacted with carbon dioxide. Among various knowndecarboxylases, pyruvic acid decarboxylase is preferred in respect ofthe relatively good versatility for various aldehyde compounds. Whencarbonate ions are reacted with acetaldehyde, for example, by utilizinga pyruvic acid decarboxylase in the presence of thiamin, the reactionproduct is pyruvic acid. When liquid carbon dioxide is reacted at 25° C.with acetaldehyde in a mixed solution of the thiamin/pyruvic aciddecarboxylase and acetaldehyde, pyruvic acid can be obtained. Theefficiency for the production of pyruvic acid by the same reaction asabove can be improved when the reaction is conducted in supercriticalcarbon dioxide.

[0013] A variety of 2-keto carboxylic acids other than pyruvic acid canbe prepared by using different combinations of the aldehyde compoundsand the decarboxylase. A preferable reaction medium in which thereaction of the invention is conducted is an alkaline buffer solutionhaving a pH value in the range from 10 to 12 or, more preferably, in thevicinity of pH 11. The reaction temperature in this case is preferablyin the range from 10 to 40° C. or, more preferably, at or in thevicinity of 25° C.

[0014] The reaction mixture after completion of the reaction in theabove-described manner can be subjected to an isolation and purificationtreatment of the 2-keto carboxylic acid as the target product by aconventional procedure of reversed-phase chromatography. When theinventive method is conducted by adequately selecting the reactionconditions, the 2-keto carboxylic acid as the purified target productcan be obtained in a yield of 50% or higher relative to the amount ofthe aldehyde compound used as the starting reactant.

[0015] In the following, the method of the present invention isdescribed in more detail by way of Examples which, however, never limitthe scope of the invention in any way.

EXAMPLE 1

[0016] A 1 ml portion of a 0.1M sodium carbonate buffer solution havinga varied pH value was admixed with acetaldehyde in a concentration of0.1 mM, thiamin in a concentration of 1 μM and 1 unit of a commerciallyavailable pyruvic acid decarboxylase and the mixture was agitated for 1hour at 25° C. to effect the enzymatic addition reaction of theacetaldehyde with the carbonate ions. The above-mentioned 1 unit of theenzyme is an amount of the enzyme capable of decarboxylating 1.0 μmoleof pyruvic acid to form acetaldehyde. After completion of the reaction,the reaction mixture was admixed with 100 μl of a 1M hydrochloric acidand then subjected to a high-performance liquid chromatographic analysisby using a silica gel column of 4.0 mm diameter and 150 mm length(Wakosil C-18AR, a product by Wako Jun-yaku Co.) at 25° C. with a 0.05%aqueous TFA (trifluoroacetic acid) solution as the eluant at a flow rateof 1 ml/minute.

[0017] The yields of the pyruvic acid product for the respective pHvalues were calculated by using a calibrati n curve pr pared in advancewith known sampl s f pyruvic acid. The r sults are shown by the barchart graph of FIG. 1 from which it is understood that the yield of thepyruvic acid depended on the pH value giving the highest yield of 62%when the pH was 11.

EXAMPLE 2

[0018] The same enzymatic addition reaction as in Example 1 wasconducted at 25° C. for 1 hour by using sodium carbonate buffersolutions in varied concentrations each having a pH of 11 in place ofthe buffer solutions having varied pH values. Each of the reactionmixtures after completion of the reaction was subjected to thehigh-performance liquid chromatographic analysis in the same manner asin Example 1 to calculate the yield of the pyruvic acid product for therespective concentrations. The results were as shown in FIG. 2 by thebar chart from which it is understood that the yield of the product wasincreased as the concentration of the buffer solution was increasedgiving the highest value of 82% with a concentration of 0.5 M within therange tested.

EXAMPLE 3

[0019] A 2 ml portion of a 0.5M tris/hydrochloric acid buffer solutionhaving a pH of 8.8 was admixed with acetaldehyde in a concentration of0.1 mM, thiamin in a concentration of 1 μM and 1 unit of the pyruvicacid decarboxylase and then admixed with 3 ml of liquefied carbondioxide. The reaction mixture was agitated for 1 hour at 25° C. underpressurization to effect the reaction. The reaction mixture aftercompletion of the reaction was subjected to the chromatographic analysisin the same manner as in Example 1 to give a result that the yield ofthe pyruvic acid product was 50%.

EXAMPLE 4

[0020] The same enzymatic addition reaction as in Example 1 was repeatedexcepting for the replacement of the acetaldehyde with the same molaramount of propionaldehyde to give a result that the product was2-ketobutyric acid in a yield of 52% when the sodium carbonate buffersolution had a pH of 11.

1. A method for the preparation of a 2-keto carboxylic acid from carbondioxide which comprises the step of: reacting carbon dioxide with analdehyde compound in the presence of a decarboxylase.
 2. The method forthe preparation of a 2-keto carboxylic acid according to claim 1 whereinthe carbon dioxide is in the form of carbonate ions.
 3. The method forthe preparation of a 2-keto carboxylic acid according to claim 1 whereinthe reaction of carbon dioxide and an aldehyde compound is conducted inan aqueous medium having a pH value in the range from 10 to
 12. 4. Themethod for the preparation of a 2-keto carboxylic acid according toclaim 1 wherein the reaction of carbon dioxide and an aldehyde compoundis conducted at a temperature in the range from 10 to 40° C.
 5. Themethod for the preparation of a 2-keto carboxylic acid according toclaim 4 wherein the reaction is conducted in a carbonate buffersolution.
 6. The method for the preparation of a 2-keto carboxylic acidaccording to claim 5 wherein the carbonate buffer solution containsthiamin.
 7. The method for the preparation of a 2-keto carboxylic acidaccording to claim 1 wherein the decarboxylase is a pyruvic aciddecarboxylase.